The purpose of this study is to elucidate key steps in the processes leading to dental caries. The major features of this disease, i.e. the involvement of specific acidogenic organisms, acid production and the comcomitant decrease in pH followed by demineralization of enamel are well established, but several critically important aspects remain unclear. Thus, the degree of saturation of plaque with respect to dental enamel is a critical determinant for the formation of carious lesions, yet factors influencing this property are incompletely investigated. Also, we propose from theoretical grounds that the relative amounts of types of acids in plaque (e.g. acetate and lactate) will have a major effect on the degree of saturation of plaque, and will therefore be important in initiation and rates of formation of carious lesions. To resolve these problems we propose, firstly, to determine pH, Ca2+, PO4-, F-, acetate, lactate and other organic acids in plaque fluid before and at selected times following its exposure to sucrose in groups of caries-resistant and caries-susceptible children. Using the obtained analytical information, the degree of saturation of the plaque fluid with respect to enamel will be calculated and correlated with caries-susceptibility. From the same data, the importance of changes in the ratio of lactate to acetate in plaque will be established. Secondly, to confirm these in vivo findings and place them on a sound theoretical basis, we will conduct in vitro demineralization experiments using extracted human teeth and demineralizing solutions mimicking the organic acid and inorganic composition of plaque fluid found to be associated with caries-resistance and caries-susceptibility. Through the use of the developed microanalytical techniques and the highly sensitive analytical instrumentation employed, the critically important microenvironment at the enamel-plaque interface will be studied. The long-term goal is to define the cariogenic potential of plaque on the basis of physical chemical principles and to demonstrate that this is specifically related to caries susceptibility in children. This work will provide a much-needed link between physical chemical factors, microbiological determinants and clinical findings involved in caries initiation and activity. This approach may ultimately be useful in the design of anti-caries procedures, in the assessment of patient risk and in the determination of relative cariogenicity of food substances.